N-nitroso compounds (nitrosamines) are potent mutagens and carcinogens in experimental animals. Although suggestive, no role has been determined in man. A chance observation while investigating amine generation in chronic renal failure pointed to a human model in uremic patients who have been reported to have an increased incidence of malignancies. This model describes the coexistence of 3 conditions for nitrosamine formation: 1) intestinal nitrates (nitrites) endogenous and exogenous (in food and water, including dialysate) 2) small intestinal secondary amines especially dimethylamine (DMA) and 3) appropriate bacterial species in same location permitting reduction of nitrate and possibly nitrosation itself, at physiologic pH and temperatures. The proposed research will identify the extent to which these three conditions exist and determine whether nitrosamine (specifically dimethylnitrosamine) is formed in vivo. If nitrosamine formation is significant a small series of patients given oral chemical inhibitors will be compared for successful inhibition of nitrosamine production. The emphasis here is on human in vivo measurement rather than on environmental pathogenesis (N-nitroso compounds in food, sewerage treatment wastes, soil, water, urban air, cigarette smoke) except as it is relevant to endogenous formation or its augmentation. Methods to be used have all been developed, some quite recently, with much of the local equipment and expertise to carry out the program. N-nitroso-compounds will be measured with gas chromatography/thermal energy analyzer, aliphatic amines by gas chromatgraphy and nitrates and nitrates by a modified Greiss method. Additionally the incidence of malignancy will be determined on a national basis in patients with end stage uremia through existing national registers and a direct questionnaire to dialysis units. Selected patients from this compilation will then be studied further. This information is particularly important in view of the federal commitment to chronic dialysis which is offered to the population at large, and which has extended their period at risk from cancer.